Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules

Liu, Shiquan; Su, Yingjie; Qin, Mengbin; Mao, Ye-Bo; Huang, Jiean; Tang, Guodu

doi:10.3892/ijo.2012.1733

Cited by 54 publications

(37 citation statements)

References 33 publications

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“…For example, SPHK1 promotes the metastasis of esophageal cancer by activating the EGFR (epidermal growth factor receptor) pathway 22 and confers malignant phenotypes in colon cancer by regulating the PTK2/FAK (protein tyrosine kinase 2) pathway 23 . EGFR activation leads to the EMT, 24 and PTK2 is necessary for the process of TGFB/TGFβ (transforming growth factor β)-induced EMT 25 .…”

Section: Discussionmentioning

confidence: 99%

SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells

Liu

et al. 2017

Autophagy

113

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SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker. Furthermore, SPHK1 accelerated the lysosomal degradation of CDH1 to induce EMT, which depended on TRAF2 (TNF receptor associated factor 2)-mediated macroautophagy/autophagy activation. In addition, the inhibition of autophagy recovered CDH1 expression and reduced cell migration and invasion through delaying the degradation of CDH1 in SPHK1-overexpressing cells. Moreover, the overexpression of SPHK1 produced intracellular sphingosine-1-phosphate (S1P). In response to S1P stimulation, TRAF2 bound to BECN1/Beclin 1 and catalyzed the lysine 63-linked ubiquitination of BECN1 for triggering autophagy. The deletion of the RING domain of TRAF2 inhibited autophagy and the interaction of BECN1 and TRAF2. Our findings define a novel mechanism responsible for the regulation of the EMT via SPHK1-TRAF2-BECN1-CDH1 signal cascades in HCC cells. Our work indicates that the blockage of SPHK1 activity to attenuate autophagy may be a promising strategy for the prevention and treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells

Liu

et al. 2017

Autophagy

113

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“…Apoptosis can be triggered by two signaling pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway) [12]. Poly(ADP-ribose) polymerase (PARP) is a key signaling nuclear protein involved in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Protects from Raddeanin A‐Induced Apoptosis in SGC‐7901 Human Gastric Cancer Cells

Teng

Liu

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Raddeanin A (RA) is an extractive from Anemone raddeana Regel, a traditional Chinese medicine. The aim of this study is to assess the efficacy of RA against human gastric cancer (GC) cells (SGC-7901) and explore its mechanism. MTT assay showed that RA inhibition of proliferation of SGC-7901 cells increased in a dose-dependent manner. Flow cytometry analysis and Hoechst 33258 staining showed that RA induced apoptosis on SGC-7901 cells. Meanwhile, it induced autophagy. Western blotting analysis showed that the RA induces apoptosis and autophagy by activating p38 MAPK pathway and inhibiting mTOR pathway. Further studies showed that autophagy inhibition could protect from RA-induced apoptosis in SGC-7901 cells. In conclusion, RA can induce SGC-7901 cell apoptosis and autophagy by activating p38 MAPK pathway. And autophagy can protect SGC-7901 cells from apoptosis induced by RA.

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“…Other studies have demonstrated that SPHK1 protein expression is unregulated in various types of cancer, including prostate cancer (13), gastric cancer (14), glioblastoma multiforme (15), intestinal adenoma (16), acute erythroleukemia (17), colon cancer (18), salivary gland carcinoma (19) and glioma (20). In addition, there is plenty of evidence indicating that activation of SPHK1 is associated with anti-apoptosis effects, and the transformation, proliferation and survival of tumor cells (21,22).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of sphingosine kinase 1 is predictive of poor prognosis in human breast cancer

et al. 2017

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Sphingosine kinase 1 (SPHK1) is a bioactive lipid mediator that has been identified as a biomarker in various cancers and is considered to play an important role in tumor progression. In the present study, the expression level of SPHK1 was examined in breast cancer clinical specimens, and its association with patient survival was investigated to clarify the clinical significance of SPHK1 in breast cancer. SPHK1 mRNA expression was increased in breast cancer tissues compared with that in matched adjacent breast tissues in 19 of 32 paired tissue specimens (59.4%). Immunohistochemical analysis of 122 breast cancer cases revealed that the expression levels of SPHK1 were upregulated in 64 tumor tissues (52.5%), and increased expression levels of the protein were significantly associated with the presence of lymph node metastasis (P=0.0016), number of positive lymph nodes (P=0.0268) and presence of distant metastasis (P=0.0097). Increased SPHK1 protein expression was also associated with human epidermal growth factor receptor 2 status (P=0.0100), initial symptoms (P=0.0025) and tumor location (P=0.0457). Patients with increased SPHK1 protein expression had shorter overall survival and disease-free survival times compared with patients with lower SPHK1. Univariate and multivariate analyses indicated that high SPHK1 expression may be a poor prognostic factor. These results indicated that SPHK1 may perform an important role in breast cancer and may be a predictive factor in patients with breast cancer.

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Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules

Cited by 54 publications

References 33 publications

SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells

SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells

Autophagy Protects from Raddeanin A‐Induced Apoptosis in SGC‐7901 Human Gastric Cancer Cells

Overexpression of sphingosine kinase 1 is predictive of poor prognosis in human breast cancer

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